The goal of this project is to determine the contributions of sex hormone levels and sex hormone-related gene variants (polymorphisms) to cognitive decline in older men and women and to compare this contribution among black and white elders. Over 33 percent of women and 20 percent of men aged 65 and older will develop dementia during their lifetime and many more will develop a milder form of cognitive impairment. Sex hormones, primarily estradiol and testosterone, may play an important role in maintenance of cognitive health. People who have low concentrations of these hormones may have more rapid cognitive decline than those with high levels. We propose to test this hypothesis by measuring serum levels of estradiol and testosterone and 4-year changes in levels in an ongoing prospective study of 3075 elderly black and white women and men. We will also determine whether physiologically-defined candidate genetic polymorphisms involved in sex hormone metabolism and hormone receptor function are associated with cognitive decline and may play an important role in maintaining cognitive function. As little is known about sex hormones and cognition in older black men and women, we will also determine if associations are similar for black and white elders. Our aims will be addressed as part of the 7- year NIH-funded Health, Aging and Body Composition (Health ABC) Study, currently finishing Year 5. The careful measurement of cognitive e function on multiple domains over 7 years, as well as having stored serum and extracted DNA, will allow for a very efficient approach to answering these questions. Further knowledge of the association between sex hormones, hormone-related polymorphisms and cognitive decline may facilitate preventative strategies to maintain independence and to promote optimum brain aging.